2-5 Intermittent Caloric Restriction for Weight Loss and Insulin Resistance in HIV-Infected Adults With Features of the Metabolic Syndrome

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Terminated

CT.gov ID

NCT03489109

Collaborator

(none)

Enrollment

Location

Arms

43.3

Actual Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Background:

Weight gain can lead to obesity and diabetes even in people living with human immunodeficiency virus (HIV). Researchers want to see if the technique intermittent calorie restriction can help overweight people with HIV as an alternative to traditional diets.

Objective:

To see if intermittent calorie restriction leads to weight loss and improved blood sugar in obese people with HIV.

Eligibility:

Adults ages 18-65 with HIV who are obese and do not have diabetes

Design:

Participants will be screened with a medical history, physical exam, and blood and urine tests.

Before starting treatment, participants will:

Have a nutritional consultation
Get a pedometer to record daily steps
Test a restricted diet for 1 day
Have a body x-ray

At the baseline visit, participants will have:

Blood drawn after they drink a sugar drink
Questions about their health and eating
A nutritional consultation
Resting energy expenditure measured. Participants will fast overnight. Then they will lie down while a plastic bubble goes over the head and a plastic sheet covers the upper body. Oxygen flows into the bubble.
Liver stiffness test. A wand on the stomach releases sound waves like an ultrasound.

For 12 weeks, some participants will be on a standard diet. Others will restrict how much food they eat 2 days a week. On those days they will eat about 25% of their recommended calories.

Participants will keep a diary of their diet and steps.

Participants will have 4 visits during the 12-week diet and 1 visit 12 weeks after the diet ends. They will repeat previous tests.

Condition or Disease	Intervention/Treatment	Phase
Human Immunodeficiency Virus Metabolic Syndrome	Behavioral: Intermittent fasting Other: Standard of Care	Phase 2

Detailed Description

The high prevalence of obesity coupled with chronic inflammation and immune activation places human immunodeficiency virus (HIV)-infected individuals at increased risk for metabolic complications emphasizing the need for more aggressive management of obesity and related co-morbidities in the aging HIV-infected population. The most effective treatment for obesity and metabolic syndrome is lifestyle modification, usually with a combination of caloric restriction and increased exercise. Intermittent caloric restriction (ICR) or intermittent fasting simplifies caloric restriction by severely limiting calories only a few days per week and allowing ad lib diet on the other days. Weight loss benefits are similar to those seen with conventional diets, however, data suggests possible added health benefits from intermittent fasting.

We propose to study the benefits of a 2-5 ICR strategy on weight, insulin resistance, and cardiovascular disease markers in obese HIV-infected adults with features of the metabolic syndrome. In a prospective pilot study, 50 HIVinfected adults will be randomized 1:1 to ICR or standard-of-care instruction of healthy diet and lifestyle for a 12-week intervention period. We hypothesize that ICR (2 days per week) will be an effective and acceptable diet strategy that will result in significant weight reduction, improvements in insulin sensitivity, and related metabolic parameters.

Study Design

Study Type:

Interventional

Actual Enrollment :

35 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

2-5 Intermittent Caloric Restriction for Weight Loss and Insulin Resistance in HIV-Infected Adults With Features of the Metabolic Syndrome

Actual Study Start Date :

May 9, 2018

Actual Primary Completion Date :

Dec 17, 2021

Actual Study Completion Date :

Dec 17, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intermittent Fasting Subject will consume approximately 25% of their daily calories for 2 days per week. The other 5 days they will eat their normal diet.	Behavioral: Intermittent fasting Subject will consume approximately 25% of their daily calories for 2 days per week. The other 5 days they will eat their normal diet
Active Comparator: Standard of Care Standard of care dietary and healthy lifestyle counseling	Other: Standard of Care Subject will receive standard of care recommendations for healthy diet and lifestyle

Arm

Intervention/Treatment

Experimental: Intermittent Fasting

Subject will consume approximately 25% of their daily calories for 2 days per week. The other 5 days they will eat their normal diet.

Behavioral: Intermittent fasting

Subject will consume approximately 25% of their daily calories for 2 days per week. The other 5 days they will eat their normal diet

Active Comparator: Standard of Care

Standard of care dietary and healthy lifestyle counseling

Other: Standard of Care

Subject will receive standard of care recommendations for healthy diet and lifestyle

Outcome Measures

Primary Outcome Measures

Change in weight and insulin sensitivity as measured by HOMA-IR [Baseline, week 12, week 24]
Weight

Secondary Outcome Measures

Tolerability of ICR [Baseline, Week 12, Week 24]
Subject's tolerability to ICR and compliance as recorded on subject diary.
Change in lipid levels, metabolic biomarkers, biomarkers of inflammation and immune activation, and mood. [Baseline, Week 12, Week 24]
Change in lipids levels, metabolic biomarkers, biomarkers of inflammation and immune activation. Mood changes measured by subject questionnaires.
Change in body composition, including visceral adiposity abd hepatic steatosis. [Baseline, Week 12, Week 24]
Change in body composition, including visceral adiposity and hepatic steatosis measured by fibroscan.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

-INCLUSION CRITERIA:

Aged 18 to 65 years
HIV RNA level less than or equal to 200 copies/mL for greater than or equal to1 year (1 measure greater than or equal to 200 allowed if also <500 and preceded and followed by one or more undetectable values)
CD4 >200 cells/mL and no active opportunistic infection or malignancy
BMI greater than or equal to 30 kg/m^2
One or more components of the metabolic syndrome as defined below.

Risk Factor: Waist circumference
Men: Defining Level: >102 cm
Women: Defining Level: >88 cm
Risk Factor: Triglycerides, greater than or equal to 150 mg/dL
Risk Factor: High density lipoprotein (HDL) cholesterol
Men: Defining Level: <40 mg/dL
Women: Defining Level: <50 mg/dL
Risk Factor: Blood pressure, greater than or equal to 130 / greater than or equal to 85 mmHg
Risk Factor: Fasting glucose, greater than or equal to 110 mg/dL

Fasting blood glucose >60 mg/dL at screening
Willingness to allow sample storage for future research
Able to provide informed consent

EXCLUSION CRITERIA:

Established diagnosis of diabetes mellitus use of anti-diabetes medications, or a Hgb A1C of >7.0%
History of eating disorder, uncontrolled mood or thought disorder, significant gastrointestinal disorder or malabsorption, or significant hepatic or renal impairment
Current use of medical therapy for overweight/obesity including phentermine, orlistat, lorcaserin, naltrexone/bupropion, and liraglutide or history of weight loss surgery. Concomitant use of medications with side effects known to potentially influence appetite are allowed if on a stable dose for at least 12 months
History of symptomatic hypoglycemia.
Use of systemic glucocorticoids (stable dose daily inhaled corticosteroid allowed)
Chronic viral hepatitis C; subjects with a history of hepatitis C successfully treated can enroll >12 months after sustained virologic response
Alcohol or substance use disorder in the past year as defined by DSM-V or positive urine drug screen
Current pregnancy, actively seeking to become pregnant or breastfeeding
Any serious health or other condition which, in the opinion of the PI or their designee, could potentially interfere with the ability of a subject to comply with the procedures and assessments of the protocol or to safely participate and complete the study.